The major aim of this proposal is to characterize the genetic organization, the biosynthesis, the polymorphism, and the immunogenic properties of melanoma associated antigens. By utilizing somatic cell hybrids, a genetic analysis of the control and expression of melanoma associated antigens will be performed and a genetical linkage will be investigated between melanoma associated antigens and other cell surface components involved in cell - cell interactions. The spatial and structural relationship of melanoma associated antigens with histocompatibility antigens will be investigated to shed some light on susceptibility to melanoma. Complement dependent, cell dependent, antibody mediated lysis tests will be utilized to investigate the biological role of alloantibodies to melanoma associated antigens. Results of these tests will be compared with those of functional tests to investigate mechanisms of escape of tumor cells to host's immune attacks. To correlate the functional properties of melanoma associated antigens with their molecular structure, antigens will be isolated from cultured melanoma cells and from body fluids by combining classical physicochemical purification procedures with immunochemical methods, utilizing anti melanoma associated antigens xenoantisera coupled to immunoadsorbents. Efforts will be made to determine the molecular structure of the smallest fragment with antigenic activity and thus to elucidate the chemical composition of allotypic sites. Methods will be developed to produce specific xenoantisera to melanoma associated antigens by means of serological and immunochemical approaches. The specificity of these reagents will be compared with that of alloantisera and antisera to Bacillus Calmette Guerin antigens which have been shown to crossreact with melanoma associated antigens. The information acquired, the methods developed, and the reagents produced in these studies will facilitate our understanding of the relationship between tumor cells and host's immune system and will be useful in developing immunodiagnostic and immunotherapeutic approaches to melanoma.